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Aims: Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high‐definition transcranial direct current stimulation (online HD‐tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double‐blind, randomized, sham‐controlled trial design. Methods: Fifty‐nine patients with schizophrenia were randomized to receive either active HD‐tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS‐FSNS). Exact low‐resolution electromagnetic tomography was used to assess the functional connectivity. Results: All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention‐to‐treat analysis, patients receiving active HD‐tDCS showed greater improvement in PANSS‐FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28–3.40), 4.28 (95% CI, 2.93–5.62), and 4.91 (95% CI, 3.29–6.52) after the intervention, as well as at 1‐week and 1‐month follow‐ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD‐tDCS was associated with a decrease in delta‐band connectivity within the default mode network. Conclusions: High‐definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting. [ABSTRACT FROM AUTHOR]

Background: Neuroticism personality trait is recognized as an important endophenotypic predictor of generalized anxiety disorder (GAD). Furthermore, endophenotype-based pathway approaches have recently been shown to have greater advantages for gene-finding strategies than traditional case-control studies. In the present study, in addition to conventional case-control methods, we used pathway analyses to test whether the tri-allelic serotonin transporter promoter polymorphism (combining 5-HTTLPR and rs25531) is associated with risk of GAD through its effects on trait neuroticism. Methods: We included 2236 Han Chinese adults in this study, including 736 patients with GAD and 1500 healthy participants. We genotyped the 5-HTTLPR and rs25531 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism method. We used the Neuroticism scale of the Maudsley Personality Inventory (MPI) short version (MPI-Neuroticism) to measure participants' tendency toward neuroticism. Results: Using endophenotype-based path analyses, we found significant indirect effects of the tri-allelic genotype on risk of GAD, mediated by MPI-Neuroticism in both men and women. Compared to women carrying the S'S' genotype, women carrying the L' allele had higher levels of MPI-Neuroticism, which in turn were associated with higher risk of GAD. Men, however, showed the opposite pattern. Using traditional case-control comparisons, we observed that the effect of tri-allelic genotype on GAD was significant, but only in women. Limitations: Participants were restricted to Han Chinese, and we used only 1 questionnaire to assess neuroticism. Conclusion: These findings are the first to show that the triallelic 5-HTTLPR polymorphism is associated with elevated risk of GAD, and that this effect is mediated via increased trait neuroticism, a sex-dependent risk pathway., Introduction Generalized anxiety disorder (GAD) is characterized by persistent worry associated with a variety of symptoms, including concentration problems, difficulty sleeping, fatigue, irritability, muscle tension and restlessness. It is a [...]

The heterogeneity of etiology may serve as a crucial factor in the challenges of treatment, including the low response rate and the delay in establishing therapeutic effect. In the present study, we examined whether social experience since early life is one of the etiologies, with the involvement of the 5-HT1A receptors, and explored the potentially therapeutic action of the subchronic administration of buspirone, a partial 5-HT1A agonist. Rats were isolation reared (IR) since their weaning, and the depressive profile indexed by the forced-swim test (FST) was examined in adulthood. Nonspecific locomotor activity was used for the IR validation. Buspirone administration (1 mg/kg/day) was introduced for 14 days (week 9–11). The immobility score of the FST was examined before and after the buspirone administration. Tissue levels of serotonin (5-HT) and its metabolite 5-HIAA were measured in the hippocampus, the amygdala, and the prefrontal cortex. Efflux levels of 5-HT, dopamine (DA), and norepinephrine (NE) were detected in the hippocampus by brain dialysis. Finally, the full 5-HT1A agonist 8-OH-DPAT (0.5 mg/kg) was acutely administered in both behavioral testing and the dialysis experiment. Our results showed (i) increased immobility time in the FST for the IR rats as compared to the social controls, which could not be reversed by the buspirone administration; (ii) IR-induced FST immobility in rats receiving buspirone was corrected by the 8-OH-DPAT; and (iii) IR-induced reduction in hippocampal 5-HT levels can be reversed by the buspirone administration. Our data indicated the 5-HT1A receptor-linked early life social experience as one of the mechanisms of later life depressive mood. [ABSTRACT FROM AUTHOR]

Background: Homicidal offenders with schizophrenia who went through psychiatric evaluations are a small but significant group during a criminal appeal. Aim: Our aims are to explore whether the types of crime, such as homicide or not, would be related to the verdicts for the alleged offenders with schizophrenia in Taiwan. Our hypothesis was that homicide cases, rather than other alleged offenses, would be more likely to be regarded as no responsibility (legal insanity) or diminished responsibility for those defendants in the forensic psychiatric evaluation opinions or the court verdicts. Methods: A retrospective comparison of the homicide offenders with the nonhomicide offenders with schizophrenia, registered between December 2000 and November 2009, was conducted in the web-based, national, open-access court verdict databank. Results: There were 33 (3.4%) in 9691 criminal homicide offenders that had a diagnosis of schizophrenia. There were 33 in the homicide group and 22 in the nonhomicide group. Among these defendants in the homicide group, 3 (9.1%) were regarded as legal insanity, and 21 (63.6%) were regarded as diminished responsibility in comparison to the zero (0%) as legal insanity and nine (40.9%) as diminished responsibility in the nonhomicide group (P = 0.029). In addition, the group with multiple evaluations tended to receive forensic psychiatric opinions as legal insanity (N = 3; 33.3%), and the group with single evaluation tended to receive forensic psychiatric opinions as diminished responsibility (N = 16; 66.67%) (P = 0.017). The group with multiple evaluations tended to be ruled as legal insanity in the court (P = 0.001). Conclusion: Homicide cases would be more likely to be regarded as legal insanity or diminished responsibility for the defendants with schizophrenia in the forensic psychiatric evaluation opinions or the court verdicts. [ABSTRACT FROM AUTHOR]